Near Infrared (NIR) spectrometry would present a high potential for on-line measurement if the robustness of multivariate calibration was improved. The lack of robustness notably appears when an ...external parameter varies—e.g. the product temperature. This paper presents a preprocessing method which aims at removing from the
X space the part mostly influenced by the external parameter variations. This method estimates this parasitic subspace by computing a PCA on a small set of spectra measured on the same objects, while the external parameter is varying. An application to the influence of the fruit temperature on the sugar content measurement of intact apples is presented. Without any preprocessing, the bias in the sugar content prediction was about 8° Brix for a temperature variation of 20 °C. After External Parameter Orthogonalisation (EPO) preprocessing, the bias is not more than 0.3° Brix, for the same temperature range. The parasitic subspace is studied by analysing the
b-coefficient of a Partial Least Square Regression (PLS) between the temperature and the influence spectra. Further work will be achieved to apply this method to the case of multiple external parameters and to the calibration transfer issue.
Near-infrared (NIR) spectroscopy is a non-destructive analytical technique that enables better-understanding and optimization of pharmaceutical processes and final drug products. The use in line is ...often limited by acquisition speed and sampling area. This work focuses on performing a multipoint measurement at high acquisition speed at the end of the manufacturing process on a conveyor belt system to control both the distribution and the content of active pharmaceutical ingredient within final drug products, i.e., tablets. A specially designed probe with several collection fibers was developed for this study. By measuring spectral and spatial information, it provides physical and chemical knowledge on the final drug product. The NIR probe was installed on a conveyor belt system that enables the analysis of a lot of tablets. The use of these NIR multipoint measurement probes on a conveyor belt system provided an innovative method that has the potential to be used as a new paradigm to ensure the drug product quality at the end of the manufacturing process and as a new analytical method for the real-time release control strategy.
Graphical abstract
Use of near-infrared spectroscopy and multipoint measurements for quality control of pharmaceutical drug products
•This technique reduces the uncertainty of sample based release procedures.•The dosage of each individual tablet can be predicted and calculated inline.•100% in-line screening applies on both R&D and ...manufacturing scale.•High throughput inline inspection can help in understanding product variability.•100% in-line inspection could fit in both “Quality by Design” or “Final Quality” concepts.
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In the scope of 100% in-line quality control and real-time release of pharmaceutical tablets, the authors present a flexible inspection module for in-line tablet analysis with integrated multipoint near-infrared (NIR) spectroscopy and 3D microwave resonance technology (3D MRT). Via an industrial case study on Diclofenac Sodium tablets, the abilities of this versatile process analytical technology (PAT) tool are presented. It is demonstrated that the combination of Diclofenac concentration prediction via NIR spectroscopy and mass prediction via 3D MRT allow to estimate the dosage of each individual tablet. Single sample repetition tests were performed on 5 tablets, measured 10 times on three different days. A high accuracy and precision of prediction was shown, with an average standard deviation below 0.5 mg. The inspection run demonstrated the added value of such inspection and sorting strategies based on the calculated dosage of individual tablets.
•First comparison study of in situ NIR and Raman spectroscopies for CHO cell cultures monitoring.•NIR and Raman spectra were recorded in parallel in the same bioreactor cultures.•Six culture ...variables including antibody concentration were monitored simultaneously.•Multivariate figures of merit were established to compare the performances of models.
For the first time, the ability of in situ Raman and Near Infrared (NIR) spectroscopies to predict in real-time the concentration of viable Chinese Hamster Ovary (CHO) cells, glucose, lactate, glutamine, ammonium and antibodies in bioreactors has been compared in parallel. PLS models were developed using Raman and NIR spectra recorded at same time points and in same cultures. Multivariate figures of merit were established to thoroughly compare the performances of models. Raman spectroscopy was found to better predict concentrations of glucose, lactate and antibody, while NIR spectroscopy predicted better glutamine and ammonium ion concentrations. By applying the models developed on spectra recorded continuously during a batch culture, both spectroscopies were able to monitor simultaneously the general trends of the concentration of different analytes, while Raman predictions were more accurate at the beginning of the culture. Moreover, other chemometric methods (partial least square regression of type 2 and spectral combination) were tested, but leading to only limited model performance improvements. Both spectroscopies are suitable tools for real-time monitoring of cell culture bioprocesses, while Raman spectroscopy provides several advantages concerning sensibility, selectivity and limit of detection. These results provide useful information for academic researchers and pharmaceutical industries to choose the most adequate spectroscopic technology for their cell culture bioprocesses.
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In-line measurements of low dose blends in the feed frame of a tablet press were performed for API concentration levels as low as 0.10% w/w. The proposed methodology utilizes the ...advanced sampling capabilities of a Spatially Resolved Near-Infrared (SR-NIR) probe to develop Partial Least-Squares calibration models. The fast acquisition speed of multipoint spectra allowed the evaluation of different numbers of co-adds and feed frame paddle speeds to establish the optimum conditions of data collection to predict low potency blends. The interaction of the feed frame paddles with the SR-NIR probe was captured with high resolution and allowed the implementation of a spectral data selection criterion to remove the effect of the paddles from the calibration and testing process. The method demonstrated accuracy and robustness when predicting drug concentrations across different feed frame paddle speeds.
Understanding the behavior of light in granular media is necessary for determining the sample size, shape, and weight when probing using fiber optic setups. This is required for a correct estimate of ...the active pharmaceutical ingredient content in a pharmaceutical blend via near-infrared spectroscopy. Several strategies to describe the behavior of light in granular and turbid media exist. A common approach is the Monte-Carlo simulation of individual photons and their description using mean free path lengths for scattering and absorption. In this work, we chose a complementary method by approximating these parameters via real physical counterparts, i.e., the particle size, shape, and density and the resulting chord lengths. Additionally, the wavelength dependence of refractive indices is incorporated. The obtained results were compared with those obtained in an experimental setup that included the SAM-Spec Felin probe head by Indatech for detecting spatially resolved spectra of samples. Our method facilitates the interpretation of the acquired experimental results by contrasting the optical response, the physical particle attributes, and the simulation results.
Organic Photo Sensor (OPS) technology allows printing on conformable plastic-like substrates complex-shaped, arbitrarily-sized and pre-aligned photosensitive elements. This article reports, to the ...best of our knowledge, the first investigation to implement this emerging technology for Multi-Angle Light Scattering (MALS) characterization of nano- and microparticle suspensions. Monte Carlo and Lorenz-Mie theory calculations as well as preliminary experimental results on latex suspensions clearly demonstrate the potential of the proposed approach.
The use of the spectral derivative method in visible and near-infrared optical spectroscopy is presented, whereby instead of using discrete measurements around several wavelengths, the difference ...between nearest neighbouring spectral measurements is utilized. The proposed technique is shown to be insensitive to the unknown tissue and fibre contact coupling coefficients providing substantially increased accuracy as compared to more conventional techniques. The self-calibrating nature of the spectral derivative techniques increases its robustness for both clinical and industrial applications, as is demonstrated based on simulated results as well as experimental data.
Fluorescence spectroscopy is a useful technique for tissue diagnostics and is also a promising tool in the characterization of embedded structures in tissue. The emitted fluorescence from an embedded ...inclusion, marked with a fluorescent compound, is affected by several factors as the light propagates through the medium to the tissue boundary, where the fluorescence light is detected. Tissue absorption, scattering and autofluorescence, as well as the size and depth of the inclusion, affect the detected fluorescence light. The aim of this study is to investigate if the size and location of a fluorescent inclusion could be determined using models based a combination of External Parameter Orthogonalisation (EPO) and Least Squares Support Vector Machine (LS-SVM). This can be very useful for data pre-processing before a full fluorescence tomography reconstruction. The data set consisted of simulated multispectral fluorescence, where depth and radius of a spherical fluorescent inclusion were varied as well as the fluorescence contrast and optical properties of the surrounding tissue. The results showed that the non-linear models based on LS-SVM can simultaneously predict both radius and depth. It was observed that EPO acts as a useful pre-processing tool on spectra for this non-linear model and that it was necessary to perform EPO to be able to predict the depth with the LS-SVM model.
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